IMM2022 Study Guide - Final Guide: Tlr 1, Tlr7, Tlr9
4 May 2018
School
Department
Course
Professor
Infection and immunity
52% of death in low income countries are
caused by infectious diseases compared to 7%
in high income countries such diseases in
pneumonia, diarrhoea and malaria that are
caused by various infectious agents.
VIRUSES
Viral structure: there are three main
components; nucleic acid, protein coat
(capsid) and +/- envelope.
Viral life cycle
1. Attachment: bind to the host receptor
2. Penetration: enter via receptor
mediated endocytosis
3. Uncoating: capsid degeneration
4. Replication: virions assembled
5. Release: lysis of budding
Anti-viral response: Innate: type I IFN and
NKC. Viral recognition is by intracellular TLRs
eg TLR3: dsDNA, TLR7: ssRNA and TLR9: CpG
DNA. NOD like receptors recognise the
products of damaged cells formation of the
inflammasome. RIG viral RNA type I IFN
response. Type I IFNs are critical in the anti-
viral response.
IFN action: binds to receptor of virally
infected cell phosphorylation of translation
initiation factor:
• Inhibition of protein synthesis
• RNAase action degradation of viral
RNA
• Inhibition of viral gene expression and
virion assembly
Type I IFNs also activate DC and NKC.
Viruses eg Herepes inhibit MHC class 1
processing and presentation. Herpes HSV
peptide interferes with the TAP transporter.
Cytomegalovirus and epstien-barr virus inhibit
the proteasome. (NKC help with these)
Adaptive: CD8+ (T-cell mediated) killing of the
virally infected cells.
In the antiviral response we need CD8 so we
have cross presentation so there is MHC class
1 presentation. CTLs kill with perforin and
granzymes.
CTLs require help from TH1s (CD4). APC
stimulate effector CD4 to induce CD40L and
IL-2. Stimulation of APC through CD40
increases B7 therefor we get Costimulation of
naïve CD8. The TH1 cytokines IFNy and IL-12
promote CTL. CTLs also secrete IFNy which
promotes the Th1. Th1 cytokines promote IgG
switching high affinity IgG in the blood can
neutralise viruses.
BACTERIA
• Pili and fimbrae to mediate adhesion
• Polysaccharide capsule – prevents
phagocytosis
• Cell wall
• Gram +: techoic acid, surface proteins,
liptechoic acid (TLF4) and PG (TLR1:2
and 2:6)
• Gram -: lipopolysacc (TLR4), surface
proteins, lipoprotein and PG (TLR1:2
and 2:6)
All PRR activation lead to NF-kB TF production
and proinflammatory cytokines eg IFN.
• IL-12 from DC acts on Th1
• IFNy from NKC acts on DC
• DC produce TNFa and IL-1
neutrophil recruitment
Phagocytes are important in the anti-bacterial
immunity. Microbes bund to the phagocyte
receptors (lectin receptor and C3 receptor).
The microbe is ingested into the phagosome,
fusion with lysosome phaglolysome. Killing
of micobes by NOS, NO and lysosomal
proteases.
Immunity varies for the type of bacteria:
Intracellular: eg M. tuberculosis, need cell
mediated. Th1 response against obligate
intracellular occurs. IFNy acts on
macrophages, TNFa and IL-1 are pro-
inflammatory. CTLs and TH1 work together to
eliminate intracellular (humoral is irrelevant)
Extracellular: need humoral IMM and Th17.
Th17 secrete Il-6 and IL-16 recruitment of
neutrophils. IL-22 epithelial barrier.
Document Summary
52% of death in low income countries are caused by infectious diseases compared to 7% in high income countries such diseases in pneumonia, diarrhoea and malaria that are caused by various infectious agents. Viral structure: there are three main components; nucleic acid, protein coat (capsid) and +/- envelope. Viral life cycle: attachment: bind to the host receptor, penetration: enter via receptor mediated endocytosis, uncoating: capsid degeneration, release: lysis of budding. Viral recognition is by intracellular tlrs eg tlr3: dsdna, tlr7: ssrna and tlr9: cpg. Nod like receptors recognise the products of damaged cells formation of the inflammasome. Rig viral rna type i ifn response. Type i ifns are critical in the anti- viral response. Ifn action: binds to receptor of virally infected cell phosphorylation of translation initiation factor: Inhibition of protein synthesis: rnaase action degradation of viral. Inhibition of viral gene expression and virion assembly. Type i ifns also activate dc and nkc.
